TLR7-mediated skin inflammation remotely triggers chemokine expression and leukocyte accumulation in the brain

Background: The relationship between the brain and the immune system has become increasingly topical as, although it is immune-specialised, the CNS is not free from the influences of the immune system. Recent data indicate that peripheral immune stimulation can significantly affect the CNS. But the mechanisms underpinning this relationship remain unclear. The standard approach to understanding this relationship has relied on systemic immune activation using bacterial components, finding that immune mediators, such as cytokines, can have a significant effect on brain function and behaviour. More rarely have studies used disease models that are representative of human disorders. Methods: Here we use a well-characterised animal model of psoriasis-like skin inflammation—imiquimod—to investigate the effects of tissue-specific peripheral inflammation on the brain. We used full genome array, flow cytometry analysis of immune cell infiltration, doublecortin staining for neural precursor cells and a behavioural read-out exploiting natural burrowing behaviour. Results: We found that a number of genes are upregulated in the brain following treatment, amongst which is a subset of inflammatory chemokines (CCL3, CCL5, CCL9, CXCL10, CXCL13, CXCL16 and CCR5). Strikingly, this model induced the infiltration of a number of immune cell subsets into the brain parenchyma, including T cells, NK cells and myeloid cells, along with a reduction in neurogenesis and a suppression of burrowing activity. Conclusions: These findings demonstrate that cutaneous, peripheral immune stimulation is associated with significant leukocyte infiltration into the brain and suggest that chemokines may be amongst the key mediators driving this response

An integrated workflow for robust alignment and simplified quantitative analysis of NMR spectrometry data

<p>Abstract</p> <p>Background</p> <p>Nuclear magnetic resonance spectroscopy (NMR) is a powerful technique to reveal and compare quantitative metabolic profiles of biological tissues. However, chemical and physical sample variations make the analysis of the data challenging, and typically require the application of a number of preprocessing steps prior to data interpretation. For example, noise reduction, normalization, baseline correction, peak picking, spectrum alignment and statistical analysis are indispensable components in any NMR analysis pipeline.</p> <p>Results</p> <p>We introduce a novel suite of informatics tools for the quantitative analysis of NMR metabolomic profile data. The core of the processing cascade is a novel peak alignment algorithm, called hierarchical Cluster-based Peak Alignment (CluPA). The algorithm aligns a target spectrum to the reference spectrum in a top-down fashion by building a hierarchical cluster tree from peak lists of reference and target spectra and then dividing the spectra into smaller segments based on the most distant clusters of the tree. To reduce the computational time to estimate the spectral misalignment, the method makes use of Fast Fourier Transformation (FFT) cross-correlation. Since the method returns a high-quality alignment, we can propose a simple methodology to study the variability of the NMR spectra. For each aligned NMR data point the ratio of the between-group and within-group sum of squares (BW-ratio) is calculated to quantify the difference in variability between and within predefined groups of NMR spectra. This differential analysis is related to the calculation of the F-statistic or a one-way ANOVA, but without distributional assumptions. Statistical inference based on the BW-ratio is achieved by bootstrapping the null distribution from the experimental data.</p> <p>Conclusions</p> <p>The workflow performance was evaluated using a previously published dataset. Correlation maps, spectral and grey scale plots show clear improvements in comparison to other methods, and the down-to-earth quantitative analysis works well for the CluPA-aligned spectra. The whole workflow is embedded into a modular and statistically sound framework that is implemented as an R package called "speaq" ("spectrum alignment and quantitation"), which is freely available from <url>http://code.google.com/p/speaq/</url>.</p

TIA-1 Cytotoxic Granule-Associated RNA Binding Protein Improves the Prognostic Performance of CD8 in Mismatch Repair-Proficient Colorectal Cancer

Evidence suggests a confounding effect of mismatch repair (MMR) status on immune response in colorectal cancer. The identification of innate and adaptive immune cells, that can complement the established prognostic effect of CD8 in MMR-proficient colorectal cancers patients, representing 85% of all cases, has not been performed

Anti-HIV-1 integrase potency of methylgallate from Alchornea cordifolia using in vitro and in silico approaches:

According to the 2018 report of the United Nations Programme on HIV/AIDS (UNAIDS), acquired immune deficiency syndrome (AIDS), a disease caused by the human immunodeficiency virus (HIV), remains a significant public health problem. The non-existence of a cure or effective vaccine for the disease and the associated emergence of resistant viral strains imply an urgent need for the discovery of novel anti-HIV drug candidates. The current study aimed to identify potential anti-retroviral compounds from Alchornea cordifolia

Título: De vitiis sermonis et glossematis latino-barbaris libro-noum.

Tit. en antep. : Opecum tomus secundus grammaticus.Marca tip. en port.Sign. : ]\p1\s *\p6\s, 2*\p4\s, A-2Z\p4\s, 3A-3N\p4\s, 30-3v\p2\s, 3X\p3\s, *-2*\p4\s, A-2Z\p4\s, 3A-3G\p4\s, 3H-3O\p2\s.Texto a dos col.Port. a dos tintas.Cada obra con port. propia

Título: Ars. historica... Historiae universalis epitome.

Tít. en antep. : "Gerardi Joan. Vossii Operum tomus quartus Historicus et Epistolicus"Marca tip. en port.Cada parte, con port. propia, y fechas de 1697 y 1698 en pie de imp.Sign. : ]\p3\s, *\p2\s, A-Z\p4\s, 2A-2E\p4\s, 2F-2I\p2\s, A-Z\p4\s, 2A-2L\p4\s, 2n-2o\p2\s, 2P\p2\s, A-O\p4\s, A-T\p4\s, A-2Z\p4\s, 3A-3D\p4\s.Texto a dos col.Port. primera a dos tintas

Título: Etymologicon linguae latinae.

Marca tip. en port.Port. común a toda la obra : "Gerardi Joan. Vossii Opera in sex tomos divisa...", tiene fecha de 1701 en pie de imp.Sign. : ]\p3\s, cruz latina]\p4\s, *\p2\s, a-b\p4\s, c-d\p4\s, ]\p1\s, A-2Z\p6\s, 3A-3L\p6\s, 3M\p5\s.Texto a dos col.Port. a dos tintas.La h. de grab. calc. : "C. Bartaeus", retrato del autor

Título: De origine ac. progressu idololatriae.

Tit. en antep. : Gerardi Joan. Vossii Operum tomus quintus de idolotria gentili.Marca tipográfica en portadas.Sign. : *-2*\p4\s, A-Z\p4\s, 2A-2Z\p4\s, 3A-3Z\p4\s, 4A-4Z\p4\s, 5A-5M\p4\s, 5N-5Z\p2\s, 6A-6C\p2\s; A-H\p4\s, I\p2\s.Texto a dos col. con filete intermedio.Port. primera a dos tintas.Contiene con port., pag. y sign. propias: R. mosis Maimonidae de Idolatria liber / cum interpretatione latina & notis Dionysii Vossi